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Key Structural Features of the Actin Filament Arp2/3 Complex Branch Junction Revealed by Molecular Simulation
Ist Teil von
Journal of molecular biology, 2012-02, Vol.416 (1), p.148-161
Ort / Verlag
England: Elsevier Ltd
Erscheinungsjahr
2012
Link zum Volltext
Quelle
Elsevier ScienceDirect Journals
Beschreibungen/Notizen
We investigated the structure, properties and dynamics of the actin filament branch junction formed by actin-related protein (Arp) 2/3 complex using all-atom molecular dynamics (MD) simulations based on a model fit to a reconstruction from electron tomograms. Simulations of the entire structure consisting of 31 protein subunits together with solvent molecules containing ∼3 million atoms were performed for an aggregate time of 175 ns. One 75-ns simulation of the original reconstruction was compared to two 50-ns simulations of alternate structures, showing that the hypothesized branch junction structure is very stable. Our simulations revealed that the interface between Arp2/3 complex and the mother actin filament features a large number of salt bridges and hydrophobic contacts, many of which are dynamic and formed/broken on the timescale of the simulation. The simulations suggest that the DNase binding loops in Arp3, and possibly Arp2, form stabilizing contacts with the mother filament. Unbiased comparison of models sampled from the MD simulation trajectory with the primary experimental electron tomography data identified regions were snapshots from the simulation provide atomic details of the model structures and also pinpoints regions where the initial modeling based on the electron tomogram reconstruction may be suboptimal.
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► We use MD simulation to study the structure and dynamics of the Arp2/3 branch junction. ► We compare two different filament models and study two different models for the active Arp2/3 complex. ► We study the atomic scale features of the actin–Arp2/3 binding interface. ► We performed unbiased comparison of models sampled from the MD simulation trajectory with the primary experimental electron tomography data to pinpoint regions where the initial modeling based on the electron tomogram reconstruction may be suboptimal.